Three-Dimensional Spheroids for Cancer Research

Tutty, Melissa Anne; Prina-Mello, Adriele

doi:10.1007/978-1-0716-3056-3_3

Cited by 5 publications

(4 citation statements)

References 199 publications

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“…These phenomena also occurred in the 4T1 and LLC cell lines, indicating a general phenomenon. Spheroids approximately 300–500μm in size have been found to best mimic in vivo tumors, specifically regarding the hypoxic zones and proliferative gradients ( 16 ). After calibrating the number of cells, our CT26-WT and CT26-NC spheroids, and even the CT26-KD 3D structures, were still within this range.…”

Section: Discussionmentioning

confidence: 99%

“…In these assays, the reduced expression of EMMPRIN inhibited cell proliferation in both monolayers and spheroids, demonstrating that EMMPRIN is involved in cell proliferation, as have been reported before in many types of cancer cells ( 49 – 51 ). Cells aggregated into spheroids are heterogeneous and consist of a proliferative outer rim and a quiescent middle layer, whereas the core is composed of necrotic cells ( 16 , 18 ). While we do not, in general, directly compare monolayers to spheroids, we note that the microenvironmental stress and the large fraction of cells that are located in the quiescent layer of the spheroid could explain the reduced proliferation rate of spheroids in general ( 52 ), and in the CT26-KD cells in spheroids in particular, compared to the same cells in monolayers.…”

Section: Discussionmentioning

confidence: 99%

“…Three-dimensional (3D) structures, such as spheroids, are closer to solid tumor in their organization and cell-cell interactions. The spherical structure creates gradients of oxygen and nutrients that generate heterogeneity in the rate of proliferation and metabolism of the spheroid cells, and in their expression of genes ( 16 , 17 ). Although these 3D structures are only an intermediate model of the tissue and do not fully model the intricate interactions between cells and their neighboring cells or the tissue-specific extracellular matrix (ECM) components ( 18 ), spheroids have become a relevant in vitro model to study the development of resistance to chemotherapeutic treatment ( 19 ) and a high throughput screening platform for drugs ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

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EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells

Feigelman,

Simanovich,

Brockmeyer

et al. 2024

Front. Immunol.

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BackgroundIn vitro studies often use two-dimensional (2D) monolayers, but 3D cell organization, such as in spheroids, better mimics the complexity of solid tumors. To metastasize, cancer cells undergo the process of epithelial-to-mesenchymal transition (EMT) to become more invasive and pro-angiogenic, with expression of both epithelial and mesenchymal markers.AimsWe asked whether EMMPRIN/CD147 contributes to the formation of the 3D spheroid structure, and whether spheroids, which are often used to study proliferation and drug resistance, could better model the EMT process and the metastatic properties of cells, and improve our understanding of the role of EMMPRIN in them.MethodsWe used the parental mouse CT26 colon carcinoma (CT26-WT) cells, and infected them with a lentivirus vector to knock down EMMPRIN expression (CT26-KD cells), or with an empty lentivirus vector (CT26-NC) that served as a negative control. In some cases, we repeated the experiments with the 4T1 or LLC cell lines. We compared the magnitude of change between CT26-KD and CT26-WT/NC cells in different metastatic properties in cells seeded as monolayers or as spheroids formed by the scaffold-free liquid overlay method.ResultsWe show that reduced EMMPRIN expression changed the morphology of cells and their spatial organization in both 2D and 3D models. The 3D models more clearly demonstrated how reduced EMMPRIN expression inhibited proliferation and the angiogenic potential, while it enhanced drug resistance, invasiveness, and EMT status, and moreover it enhanced cell dormancy and prevented CT26-KD cells from forming metastatic-like lesions when seeded on basement membrane extract (BME). Most interestingly, this approach enabled us to identify that EMMPRIN and miR-146a-5p form a negative feedback loop, thus identifying a key mechanism for EMMPRIN activities. These results underline EMMPRIN role as a gatekeeper that prevents dormancy, and suggest that EMMPRIN links EMT characteristics to the process of spheroid formation.ConclusionsThus, 3D models can help identify mechanisms by which EMMPRIN facilitates tumor and metastasis progression, which might render EMMPRIN as a promising target for anti-metastatic tumor therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells

Feigelman,

Simanovich,

Brockmeyer

et al. 2024

Front. Immunol.

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“…128 Some research revealed that cells in multicellular tumor spheroids (MCTS) are similarly or even more vulnerable to anticancer drugs than their 2D monolayer counterparts, despite the majority of studies demonstrating that cells in spheroids are more chemoresistant than cells in 2D monolayers. 129 For instance, it was demonstrated that both tumor cells grown in monolayer cell culture and tumor cells grown as multicellular spheroids were susceptible to the proteasome inhibitor PS-341's effects. 130 Spheroids are also more radioresistant than 2D monolayers, according to a number of studies.…”

Section: Application Of Printable Biomaterials For Cancer Therapymentioning

confidence: 99%